This invention relates to the chiral, total synthesis of thienamycin from D-glucose (dextrose).
In its broadest terms, the process proceeds from glucose via intermediates I, II, and III and encounters aldehyde IV which is known to be useful in the total synthesis of thienamycin (V). ##STR2## wherein: R.sup.2 is hydrogen or a removable protecting group such as a triorganosilyl group wherein the organo moieties are independently selected from alkyl having 1-6 carbon atoms, phenyl, and aralkyl having 7-14 carbon atoms; R.sup.1 is a lower alkyl having 1-6 carbon atoms, or aralkyl, for example, methyl, ethyl, propyl, benzyl, and the like; R is lower alkyl or the two sulfur atoms may be joined to form a ring comprising R.
The transformation IV.fwdarw.V is known. See, for example, U.S. patent application Ser. No. 112,058 filed Jan. 14, 1980. To the extent that the cited U.S. patent application discloses the utility of intermediate species IV and its transformation to thienamycin, it is hereby incorporated by reference. Also incorporated by reference for the same purpose are U.S. Pat. No. 4,234,596 (issued Nov. 18, 1980); and EPO Application No. 79101307.1 filed May 1, 1979, Publication No. 0007973.
Also incorporated by reference are the following concurrently filed, commonly assigned U.S. patent applications of Philippe L. Durette Ser. No. 248,175, now pending, Ser. No. 248,178, now U.S. Pat. No. 4,348,325 issued Sept. 7, 1982; Ser. No. 248,176, now U.S. Pat. No. 4,324,900 issued Apr. 13, 1982 and Ser. No. 248,174 now abandoned (all filed Mar. 30, 1981). [Merck & Co., Inc., all filed Mar. 30, 1981]. All of these applications relate to the synthesis of thienamycin from D-glucose.
As will be made evident from the Detailed Description of the Invention which follows, the presently disclosed and claimed process is characterized by several advantages. Most noteworthy is that the starting reagents for the process are inexpensive and safe to handle. The process is characterized by being conducted under moderate conditions which are amenable to scale up and by a sequence of steps which are individually high yielding. It should be further noted that in many of the sequences the intermediates need not be isolated so that individual sequences or distinct process steps may be conducted in a single pot.